dbSNP rs2304935: MS4A6E:p.Ile6Val (chr11-60334911-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139249.4(MS4A6E):c.16A>G(p.Ile6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,609,964 control chromosomes in the GnomAD database, including 89,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8425 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81433 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.775

Publications

28 publications found

Variant links:

Genes affected

MS4A6E (HGNC:14285): (membrane spanning 4-domains A6E) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. The gene encoding this protein is localized to 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

MS4A6E links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_139249.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.984567E-5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139249.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MS4A6E	NM_139249.4	MANE Select	c.16A>G	p.Ile6Val	missense	Exon 2 of 5	NP_640342.1	Q96DS6
MS4A6E	NR_170614.1		n.184A>G		non_coding_transcript_exon	Exon 2 of 6
MS4A6E	NR_170615.1		n.184A>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MS4A6E	ENST00000684409.1	MANE Select	c.16A>G	p.Ile6Val	missense	Exon 2 of 5	ENSP00000507799.1	Q96DS6
MS4A6E	ENST00000300182.8	TSL:1	c.16A>G	p.Ile6Val	missense	Exon 1 of 4	ENSP00000300182.4	Q96DS6
MS4A6E	ENST00000969922.1		c.16A>G	p.Ile6Val	missense	Exon 3 of 6	ENSP00000639981.1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48590

AN:

151926

Hom.:

8403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.324

AC:

81521

AN:

251412

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.326

AC:

475580

AN:

1457920

Hom.:

81433

Cov.:

AF XY:

0.321

AC XY:

232571

AN XY:

725490

show subpopulations

African (AFR)

AF:

0.249

AC:

8327

AN:

33428

American (AMR)

AF:

0.378

AC:

16891

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6586

AN:

26108

East Asian (EAS)

AF:

0.299

AC:

11847

AN:

39688

South Asian (SAS)

AF:

0.149

AC:

12836

AN:

86182

European-Finnish (FIN)

AF:

0.544

AC:

29056

AN:

53408

Middle Eastern (MID)

AF:

0.192

AC:

1104

AN:

5764

European-Non Finnish (NFE)

AF:

0.334

AC:

370683

AN:

1108346

Other (OTH)

AF:

0.303

AC:

18250

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

14824

29649

44473

59298

74122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11878

23756

35634

47512

59390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.320

AC:

48655

AN:

152044

Hom.:

8425

Cov.:

AF XY:

0.328

AC XY:

24367

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.252

AC:

10439

AN:

41470

American (AMR)

AF:

0.362

AC:

5534

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

935

AN:

3468

East Asian (EAS)

AF:

0.265

AC:

1370

AN:

5174

South Asian (SAS)

AF:

0.151

AC:

727

AN:

4826

European-Finnish (FIN)

AF:

0.570

AC:

6011

AN:

10538

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22706

AN:

67978

Other (OTH)

AF:

0.295

AC:

623

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1653

3306

4958

6611

8264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.315

Hom.:

26338

Bravo

AF:

0.304

Asia WGS

AF:

0.224

AC:

778

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0060

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.00025

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.25

MetaRNN

Benign

0.000070

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.69

PhyloP100

-0.78

PrimateAI

Benign

0.30

PROVEAN

Benign

0.23

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

PromoterAI

0.041

Neutral

(source)

Varity_R

0.016

gMVP

0.071

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over